Evaluation of Strength Reduction Factor for Concentrically Braced Frames Based on Nonlinear Single Degree-of-Freedom Systems

Strength Reduction Factor (R-Factor), often referred to as Response Modification Factor, is commonly used in the design of lateral force resisting systems under seismic loading. R-Factors allow for a reduction in design base shear demands, leading to more economical designs. The reduction of strength is remedied with ductile behavior in members of proper detailing. Modern seismic codes and provisions recommend R-Factors for many types of lateral force resisting systems. However these factors are independent of the system fundamental frequency and many other important system properties, resulting in factors that may result in an unfavorable seismic response. To evaluate the validity of prescribed R-Factors an extensive analytical parameter study was conducted using a FEM single degree-of-freedom Concentrically Braced Frame (CBF) under incremental dynamic analysis over a suite of ground motions. Parameters of the study include brace slenderness, fundamental frequency, increment resolution, FEM mesh refinement, effects of leaning columns, and effects of low-cycle fatigue. Results suggest that R-Factor can vary drastically for CBF systems with differing properties

ADVANCEMENTS IN THE CHARACTERIZATION OF STABILITY LIMIT STATES FOR STEEL I-SECTION MEMBERS SUBJECTED TO FLEXURE

This research addresses various fundamental advancements in the calculation of the strength of steel I-section members subjected to flexure. I-section members classify as thin-walled open-sections having a relatively low lateral flexural rigidity EIy, Saint Venant torsional rigidity GJ, and warping rigidity ECw, relative to the stiffness in major-axis bending. These characteristics make I section members susceptible to lateral-torsional buckling (LTB). In the United States (US), design specifications classify the strength of steel I-section members through a LTB curve that is subdivided into three regions. The first region is referred to as the “plateau” where out-of-plane bracing is sufficient such that the member can fully develop its cross-section strength. The third region corresponds to theoretical elastic LTB. The second (middle) region corresponds to an out-of-plane failure but where significant yielding of the cross section occurs prior to the strength limit. This region is represented by a linear interpolation between anchor points corresponding to the elastic buckling and the plateau strengths. Proper determination of the anchor points at the transition between the plateau and the inelastic buckling regions, (Lp, Mmax), and between the inelastic and elastic buckling regions, (Lr, ML), requires consideration of results from beam theory, numerical modeling, and experimental testing. This research develops the fundamental basis for, and creates various improvements to, the design of general built-up I-section members within the primary US (AISC and AASHTO) standards. These improvements provide: (1) calculated capacities that better fit new and existing data via changes to the anchor points (Lp, Mmax) and (Lr, ML); (2) increases in calculated capacities recognizing inelastic reserve strength in members experiencing early yielding in flexural tension; and (3) substantial shortening and streamlining of Specification provisions for design. Improvements in the characterization of the LTB strength curves are carried forward to calculation of the resistance of general nonprismatic I-section members subjected to flexure. This research presents a two-part methodology for calculating the strength of any general nonprismatic member through (1) the calculation of the elastic buckling resistance, via manual or numerical procedures; and (2) mapping the elastic buckling resistance to a nominal member capacity.Ph.D

Increased Stathmin1 Expression in the Dentate Gyrus of Mice Causes Abnormal Axonal Arborizations

Pituitary adenylate cyclase-activating polypeptide (PACAP) is involved in multiple brain functions. To clarify the cause of abnormal behavior in PACAP deficient-mice, we attempted the identification of genes whose expression was altered in the dentate gyrus of PACAP-deficient mice using the differential display method. Expression of stathmin1 was up-regulated in the dentate gyrus at both the mRNA and protein levels. PACAP stimulation inhibited stathmin1 expression in PC12 cells, while increased stathmin1expression in neurons of the subgranular zone and in primary cultured hippocampal neurons induced abnormal arborization of axons. We also investigated the pathways involved in PACAP deficiency. Ascl1 binds to E10 box of the stathmin1 promoter and increases stathmin1 expression. Inhibitory bHLH proteins (Hes1 and Id3) were rapidly up-regulated by PACAP stimulation, and Hes1 could suppress Ascl1 expression and Id3 could inhibit Ascl1 signaling. We also detected an increase of stathmin1 expression in the brains of schizophrenic patients. These results suggest that up-regulation of stathmin1 in the dentate gyrus, secondary to PACAP deficiency, may create abnormal neuronal circuits that cause abnormal behavior

Dissecting strategies to tune the therapeutic potential of SARS-CoV-2–specific monoclonal antibody CR3022

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coupled with a lack of therapeutics, has paralyzed the globe. Although significant effort has been invested in identifying antibodies that block infection, the ability of antibodies to target infected cells through Fc interactions may be vital to eliminate the virus. To explore the role of Fc activity in SARS-CoV-2 immunity, the functional potential of a cross–SARS-reactive antibody, CR3022, was assessed. CR3022 was able to broadly drive antibody effector functions, providing critical immune clearance at entry and upon egress. Using selectively engineered Fc variants, no protection was observed after administration of WT IgG1 in mice or hamsters. Conversely, the functionally enhanced Fc variant resulted in increased pathology in both the mouse and hamster models, causing weight loss in mice and enhanced viral replication and weight loss in the more susceptible hamster model, highlighting the pathological functions of Fc-enhancing mutations. These data point to the critical need for strategic Fc engineering for the treatment of SARS-CoV-2 infection

DNA vaccine protection against SARS-CoV-2 in rhesus macaques

The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates